a Department of Orthopaedics , Affiliated Hospital of Nantong University , Nantong , Jiangsu Province , China.
b Research Center of Clinical Medicine, Affiliated Hospital of Nantong University , Nantong , Jiangsu Province , China.
Immunopharmacol Immunotoxicol. 2018 Apr;40(2):179-185. doi: 10.1080/08923973.2018.1424901. Epub 2018 Jan 19.
Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and cobalt ions (Co) are the most serious adverse effect in the patients with metal-on-metal hip prostheses. Therefore, an urgent need exists for the identification of the mechanisms and the development of therapeutic strategies to limit it.
We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co and developed strategies to reduce this cytotoxicity with α-tocopherol treatment.
To evaluate the protective effect of α-tocopherol, Balb/3T3 cells were pretreated with 10 μM α-tocopherol for 24 h. The cells were then exposed to different concentrations of CoNPs and Co for 12 h, 24 h and 48 h. The cell viabilities, reactive oxygen species (ROS), inflammatory cytokines and MAP kinase (MAPK) levels were measured.
CoNPs and Co can induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, α-tocopherol pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co, decrease ROS production and decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK pathway may be involved in the protection of α-tocopherol against cytotoxicity induced by CoNPs and Co in vitro.
Our results provide new insights into the potential therapeutic use of α-tocopherol in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries.
目前，金属对金属髋关节假体患者中钴纳米颗粒（CoNPs）和钴离子（Co）引起的组织损伤是最严重的不良效应。因此，迫切需要确定机制并开发治疗策略来限制这种细胞毒性。
我们旨在探讨 CoNPs 和 Co 的细胞毒性机制，并通过α-生育酚治疗开发减少这种细胞毒性的策略。
为了评估 α-生育酚的保护作用，Balb/3T3 细胞用 10 μM α-生育酚预处理 24 h。然后，将细胞暴露于不同浓度的 CoNPs 和 Co 12 h、24 h 和 48 h。测量细胞活力、活性氧（ROS）、炎症细胞因子和丝裂原活化蛋白激酶（MAPK）水平。
CoNPs 和 Co 可诱导 Balb/3T3 细胞中 ROS 和炎症细胞因子（如肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6））的增加。然而，α-生育酚预处理可显著预防 CoNPs 和 Co 诱导的细胞毒性，减少 ROS 产生并降低 Balb/3T3 细胞中炎症细胞因子的水平。此外，MAPK 通路可能参与了 α-生育酚对 CoNPs 和 Co 体外诱导的细胞毒性的保护作用。
我们的结果为 α-生育酚在预防和治疗各种氧化或炎症应激相关炎症和损伤中的潜在治疗用途提供了新的见解。
